Background: Cardiovascular diseases may be linked to dementia pathogenesis. The cardio‐autonomic control (CAC) plays an important role in the development of cardiovascular diseases and may be implicated by dementia pathophysiology. We tested whether the CAC proxied by the complexity of beat‐to‐beat pulse rate intervals (PRI) predicted longitudinal cognitive decline in older adults.Method: Continuous overnight pulse oximetry (photoplethysmography) data from 594 participants (mean age = 82.76±7.11 at oximetry assessment; 76% female) in the Rush Memory and Aging projects were studied. All participants completed cognitive assessments at oximetry baseline. Eighty‐four participants who had at least one follow‐up cognitive assessment were included in the analyses. After quality control, the feet of pulse waves in the photoplethysmography data were detected, and the consecutive foot‐to‐foot internals (i.e., PRI) time‐series within each 10‐min window were analyzed using the distribution entropy that evaluated the complexity of PRI (i.e., greater distribution entropy means more complex dynamics). To reduce behavioral and circadian effects, we used the mean distribution entropy values during 12AM‐3AM for each individual. Mixed‐effects models were constructed to associate distribution entropy to longitudinal cognitive changes, adjusting for age, sex, and education.Result: At baseline, distribution entropy was normally distributed (mean = 0.33±0.14). On average, the global cognition score was 0.12 units (SD = 0.60). This score declined at an annual rate of 0.15 units (SE = 0.04; p = 0.0001). The distribution entropy was not associated with global cognition at baseline, but greater distribution entropy predicted slower cognitive decline. Specifically, a 1‐SD increase in distribution entropy correlated with a drop of 0.11 (SE = 0.04; p = 0.005) in the rate of cognitive decline.Conclusion: The nighttime CAC (potentially during sleep) is linked with longitudinal cognitive profiles in older adults. As the CAC is regulated by an internal body clock—the circadian system, in which a dysfunction is involved in Alzheimer’s pathogenesis, it is possible that the CAC underlies the connections of cardiovascular disorders and circadian dysfunction with Alzheimer’s disease and its clinical outcomes. Future studies are warranted to test these hypotheses. Further studies should also investigate whether CAC at different times of the night has different correlations with cognitive changes and whether CAC predicts Alzheimer’s disease.